Pharmacogenetic Effects of Inhaled Salbutamol on 10-km Time Trial Performance in Competitive Male and Female Cyclists.

OBJECTIVE: To determine the effects of single nucleotide polymorphisms (SNPs) in the adrenergic ß2-receptor gene (ADRB2, rs1042713, and rs1042714) and epithelial Na channel gene (SCNN1A, rs2228576) on cycling performance after the inhalation of salbutamol. DESIGN: Randomized double-blind, mixed-model repeated measures. SETTING: University Research Setting. PARTICIPANTS: Sixty-nine trained (maximal oxygen consumption: 62.3 ± 7.6 mL·kg·min) male and female cyclists, aged 19 to 40 years. INTERVENTIONS: Participants performed two 10-km time trials 60 minutes after the inhalation of 400 µg of salbutamol or placebo. Subjects were genotyped for the three SNPs (rs1042713: AA 8, AG 30 GG 31; rs1042714: CC 19, CG 35, GG 15; rs2228576: GG: 31 GA: 34 AA: 4). MAIN OUTCOME MEASURES: Forced expiratory volume in 1 second (FEV1) was assessed immediately before and 30 minutes after inhalation. Performance was measured by mean power output maintained over the duration of the time trial. RESULTS: There was a significant increase in FEV1 after the inhalation of salbutamol [mean (SD) = 5.68% (4.7)] compared with placebo [0.84% (2.8); P < 0.001]; however, this did not lead to an improvement in 10-km cycling time trial performance. Neither the bronchodilatory response nor the time trial performance after salbutamol was affected by genotype at any of the 3 SNPs. CONCLUSIONS: In cyclists, FEV1 was significantly improved after salbutamol administration regardless of genotypic variation at the ADRB2 (rs1042713 and rs1042714) and SCNN1A (rs2228576) genes. Despite this improvement in lung function, 10-km time trial performance was not altered after the inhalation of salbutamol. CLINICAL RELEVANCE: Our findings did not show genotype-dependent differences in bronchodilatory responses and athletic performance to inhaled salbutamol, suggesting that genotype-specific drug therapy will not improve asthmatic athletes' care nor athletic performance.

Inhaled salbutamol does not affect athletic performance in asthmatic and non-asthmatic cyclists.

RATIONALE: Salbutamol may affect lung function and exercise performance differently in individuals with and without asthma. OBJECTIVES: To compare the effects of inhaled salbutamol on lung function, exercise performance and respiratory parameters during cycling exercise in athletes with a positive response to a eucapnic voluntary hyperpnoea (EVH+) and negative (EVH-) challenge, indicative of exercise-induced bronchoconstriction. METHODS: In a randomised controlled trial with a crossover design, a total of 49 well-trained male athletes (14 EVH+ and 35 EVH-) performed two simulated 10 km time-trials on a cycle ergometer 60 min after the inhalation of either 400 µg of salbutamol or a placebo. Lung function, assessed by forced expiratory volume in 1 s, was measured immediately before and 30 min after inhalation. Performance was measured by mean power output. MEASUREMENTS & MAIN RESULTS: Despite a significant increase in lung function after the inhalation of salbutamol compared to the placebo (p<0.001), salbutamol did not affect athletes' perceptions of dyspnoea (p>0.05) or leg exertion (p>0.05) during exercise. Salbutamol did not affect mean power output: EVH+ and EVH- athletes averaged 4.0 (0.5) and 4.1 (0.5) W/kg after salbutamol and 4.0 (0.5) W/kg and 4.0 (0.4) W/kg after placebo, respectively (p>0.05 for each comparison). CONCLUSIONS: The inhalation of salbutamol induced a significant increase in resting lung function in EVH+ and EVH- athletes but this improvement in lung function did not translate to improved exercise performance. Salbutamol had no discernible effect on key ventilatory and exercise parameters regardless of EVH challenge outcome.

A DNA-based method for detecting homologous blood doping.

Homologous (or allogeneic) blood doping, in which blood is transferred from a donor into a recipient athlete, is the easiest, cheapest, and fastest way to increase red cell mass (hematocrit) and therefore the oxygen-carrying capacity of the blood. Although thought to have been rendered obsolete as a doping strategy by the increased use of rhEPO to increased hematocrits, there is evidence that athletes are still using this potentially dangerous method to improve endurance performance. Current testing for homologous blood doping is based on identification of mixed populations of red blood cells by flow cytometry. This paper proposes that homologous blood doping could also be tested for by high-resolution qPCR-based genotyping and demonstrates that assays could be developed that would detect second populations of cells even if the "donor" blood was depleted of 99% of the DNA-containing leukocytes. Issues of test specificity and sensitivity are discussed as well as some of the ethical considerations that would have to be addressed if athletes' genotypes were to be used by the anti-doping authorities to prevent, or detect, the use of prohibited ergogenic practices.

Experiential versus genetic accounts of inactivity: implications for inactive individuals' self-efficacy beliefs and intentions to exercise.

The overall purpose of this study was to examine the effect of deterministic media reports, linking genetics to inactivity, in relation to inactive people's social cognitions concerning physical activity involvement. Sixty three inactive university students were randomly allocated to one of three experimental conditions (control, genetically-primed, experientially-primed) and completed measures of instrumental and affective attitudes, subjective norms, self-efficacy, and exercise intentions. One week later participants in the two experimental conditions were provided with a bogus newspaper report that either reflected a genetic explanation for physical inactivity or an experiential basis for inactivity. Shortly afterwards, participants in all three conditions completed the same measures as at pre-test. The results revealed that after controlling for baseline measures participants in the experientially-primed condition reported significantly higher levels of self-efficacy and intentions to exercise than those in the genetically-primed condition. These findings raise a cautionary flag concerning the presentation of genetic research in the media, especially with regard to inactive populations.

Genitals to genes: the history and biology of gender verification in the Olympics.

From 1968 to 1998, female Olympic athletes were expected to prove their "femininity," ostensibly to stop male "ringers" from passing themselves off as female competitors. Rumours that men were competing in drag had been around since at least the 1936 games. The sex tests started out as simple anatomical examinations--the "nude parade," but rapidly progressed to cellular-based tests (the presence of a Barr body), and eventually to molecular-based tests (the absence of the SRY gene). Women went from being defined by genitalia to cellular characteristics, and finally, by genotype but ironically, as the tests become more sophisticated, both sensitivity and specificity suffered. This paper reviews the science underlying the sex tests, their history, and the controversy that accompanied them.

Effects of intermittent hypoxia on the cerebrovascular responses to submaximal exercise in humans.

Intermittent hypoxia (IH) has been shown to alter the ventilatory and cardiovascular responses to submaximal exercise; however, the effect of IH on the cerebral blood flow (CBF) response to submaximal exercise has not been determined. This study tested the hypothesis that IH would blunt the CBF response during eucapnic and hypercapnic exercise. Nine healthy males underwent 10 consecutive days of isocapnic IH (oxyhaemoglobin saturation = 80%, 1 h day(-1)). Ventilatory, cardiovascular, and cerebrovascular responses to cycle exercise (50, 100, and 150 W) were measured before and after IH. Carbon dioxide (5% CO(2)), a mediator of CBF during exercise, was administered for 2 min of each exercise stage. Over the 10 days of IH, there was an increase in minute ventilation [Formula: see text] during the IH exposures (P < 0.05). Although exercise produced increases in [Formula: see text] middle cerebral artery mean velocity (MCA V (mean)), and mean arterial pressure (P < 0.05), there was no effect of IH. Similarly, hypercapnic exercise increased [Formula: see text] and MCA V (mean) (P < 0.05); however, the magnitude of the response was unchanged following IH. Our findings indicate that ten daily hypoxia exposures does not alter the CBF response to submaximal exercise.

Hypoxia and environmental epigenetics.

Epigenetics refers to long-term modifications of gene activity that can be inherited, either somatically or transgenerationally, but that are independent of alterations in the primary base sequence of the organism's DNA. These changes can include chemical modifications of both the DNA bases and the proteins that associate with the DNA helices to form chromatin, the nucleic acid:protein complex of which the chromosomes are comprised. Epigenetic modifications can affect the accessibility of the DNA for transcription factors (the DNA-binding proteins that specify which genes are to be active or silent by modulating the recruitment of the transcriptional machinery that reads the information encoded in the sequence) and thereby regulate the expression of genes and alter the phenotype of the organism. Epigenetic marks can also be re-established following mitosis, allowing patterns of differential gene expression to be transmitted from one cell generation to the next, and can even be maintained through meiosis, allowing transgenerational transfer of regulatory cues. Unlike the information encoded in the DNA sequence, which is invariant between most cell types and over time, epigenetic information is tissue specific and can change in response to exogenous and endogenous perturbations. This responsive capacity enables a sensitive and reactive system that can optimize gene expression in relevant tissue in response to environmental change. The realization that organisms are capable of genetically 'reprograming' themselves as well as 'preprograming' future cells, and even future offspring to optimize gene expression for a given environment may have tremendous ramifications on our understanding of both acclimatization and adaptation to hypoxia.

Haematological acclimation and re-acclimation to hypoxia in the mouse.

Haematological responses throughout 4 w of initial acclimation (IA) and three paradigms of re-acclimation (RA) to hypoxia (FI(O2)) were examined in female mice. We hypothesised that (i) haematological responses would be increased during re-exposure, resulting in greater O2-carrying capacity in RA compared to IA; and (ii) further improvements would occur when abbreviating the de-acclimation period to 1 w (RA↓DA) or extending the IA period to 8 w (RA↑IA). The serum [EPO] response was blunted in all RA groups compared to IA but the resulting reticulocyte response was similar in all experimental groups. The [Hb] response was the same in RA and RA↓DA as in IA but was blunted in RA↑IA due to a reduction in mean corpuscular Hb. The sensitivity of EPO-producing cells appears blunted but the sensitivity of erythroid precursors to EPO is enhanced by recent hypoxic exposure. Erythropoietic regulation is altered during RA in a manner that is dependent on the paradigm of initial exposure.

A mouse atlas of gene expression: large-scale digital gene-expression profiles from precisely defined developing C57BL/6J mouse tissues and cells.

We analyzed 8.55 million LongSAGE tags generated from 72 libraries. Each LongSAGE library was prepared from a different mouse tissue. Analysis of the data revealed extensive overlap with existing gene data sets and evidence for the existence of approximately 24,000 previously undescribed genomic loci. The visual cortex, pancreas, mammary gland, preimplantation embryo, and placenta contain the largest number of differentially expressed transcripts, 25% of which are previously undescribed loci.